1. Field of the Invention
This invention relates, generally, to tumor resistance. More particularly, it relates to a noninvasive evaluation of tumor resistance using sodium and/or diffusion magnetic resonance imaging (MRI).
2. Description of the Prior Art
Tumor resistance is typically determined after a course of therapy, following an extended period of drug administration. It is well known that during tumor progression, especially after therapeutic interventions, the tumor may become more resistant to therapies; consequently, the tumor requires a much higher concentration of a chemotherapeutic drug to achieve the same level of response, or the chemotherapy may be rendered ineffective. Drug intervention itself can make a tumor even more resistant than the tumor was prior to drug intervention. Thus, it would be important to have the capability to evaluate tumor resistance promptly and noninvasively prior to drug therapy.
Currently, a biopsy is the conventional technology used to deliver information on tumor resistance prior to therapy. The procedure for biopsy is invasive, as tumor cells must be extracted. This is often a complicated procedure, and not all patients may agree to undergo it. Tumor cells must be extracted from biopsy tissue. Cells are then cultivated in the presence of a selected drug to determine the level of tumor cell resistance to that drug.
However, the biopsy process may take approximately four days to achieve the results desired regarding tumor resistance. There are also the added expenses of labor and equipment to perform the biopsy.
Moreover, handling any in vitro cancer cell can itself change the evaluated tumor resistance. Reproducibility and accuracy of in vitro assays are strongly dependent on multiple factors, including cancer cell aggregation, life span of the chemotherapeutic drug, tissue handling, and conditions of cell cultivation. Consequently, the results of evaluation may be only indicative but not quantitative.
Additionally, a biopsy is not always an acceptable option, for example in the case of brain tumors. Moreover, cells in one part of a tumor can have a different level of resistance compared to another region of the same tumor. Even taking multiple biopsy samples is unlikely to fully reveal the heterogeneous nature of large tumors.
Positron emission tomography (PET) is another option that has the potential for evaluating tumor cell resistance. It relies on cancer cell glycolytic metabolic activity. Currently, it is only expected that PET could be useful for diagnosis of tumor resistance. Disadvantages of such assays include administration of radioactive materials to patients and the cost of PET analyses. PET yields low-resolution images and must be combined with computer tomography to obtain any anatomical localization of the tumor. The results of PET are also strongly affected by multiple technical, biological and physical factors, thus creating the potential of inaccurate results.
Many cancers quickly develop mechanisms enabling them to evade chemotherapeutic interventions. The adaptive changes are inevitable during tumor development even after minor variations in environmental factors such as medication and diet. Large changes are especially evident after drug interventions. Thus, the typical therapy applied to the same type of tumor and at the same anatomical place may not be successful because of unavoidable mounting resistance. Reliable methods for determining drug resistance in advance of therapy do not yet exist.
Accordingly, what is needed is a prompt, noninvasive and individualized evaluation of tumor resistance. However, in view of the art considered as a whole at the time the present invention was made, it was not obvious to those of ordinary skill how the art could be advanced.
While certain aspects of conventional technologies have been discussed to facilitate disclosure of the invention, Applicants in no way disclaim these technical aspects, and it is contemplated that the claimed invention may encompass one or more of the conventional technical aspects discussed herein.
The present invention may address one or more of the problems and deficiencies of the prior art discussed above. However, it is contemplated that the invention may prove useful in addressing other problems and deficiencies in a number of technical areas. Therefore, the claimed invention should not necessarily be construed as limited to addressing any of the particular problems or deficiencies discussed herein.
In this specification, where a document, act or item of knowledge is referred to or discussed, this reference or discussion is not an admission that the document, act or item of knowledge or any combination thereof was at the priority date, publicly available, known to the public, part of common general knowledge, or otherwise constitutes prior art under the applicable statutory provisions; or is known to be relevant to an attempt to solve any problem with which this specification is concerned.